Mito is difficult to diagnose as symptoms can range from mild to severe and can impact many different organs and body systems. The most severe forms of mito can lead to mortality or significant disability.

Currently the treatment options for mito are limited so preventative options are very important to avoid the devastating impacts on individuals and families.

Some options are available at the moment for women who are planning a family and are at increased risk of having a child with mito. Pre-implantation genetic diagnosis (PGD) and in-vitro fertilisation (IVF) using donated eggs are possibilities but PGD is not suitable for women at high risk of having a child with mito. Another option may be on the horizon for couples to have children who are genetically related to both parents; mitochondrial donation.

The technique involves replacing the mitochondrial DNA in the mother’s egg with DNA from a donor egg. This represents less than 0.1% of the mother’s genetic material that is being passed on to her baby, but when a mother has a high risk of passing on mutated mitochondrial DNA, this could save her child from a potentially life-threatening or highly debilitating illness.

Currently the practice is illegal in Australia as it contravenes laws against cloning and research involving human embryos. However, in June 2018 the Senate Community Affairs References Committee recommended that the government begin taking steps towards potentially legalising mitochondrial donation.

Professor David Thorburn is co-Group Leader of Brain & Mitochondrial Research at the Murdoch Children’s Research Institute and has worked on mito for over 25 years. He is also a founding director of the Mito Foundation and the Chair of their Scientific & Medical Advisory Panel. We asked Prof Thorburn some questions about mitochondrial donation.

1. How does a woman know she is a carrier of mito?

Most women don’t know they have a chance to pass on mito. Some families have strong maternal histories with multiple cases of mito being passed down maternal lines so the risk is clear. Some women may also have found out about their mito risk after having a child die in infancy. Sometimes a woman may have a child with severe mito and then had genetic testing herself for mutations. On closer questioning and investigation doctors may uncover symptoms in the mother that were not previously attributed to mito such as problems with sight, mild hearing loss or exercise intolerance. More often than not there is no known family history.

2. Can women be screened before conception?

It is possible for women at high risk, who have a family history of mito to be screened. As with most other genetic diseases we do not have broad population screening.

This is in part because it is much harder to screen for mitochondrial DNA as some mutations can disappear from the blood with age so would not show up on a blood test. We can use a muscle biopsy to test for mito but this is more invasive so we often test urine as the mutation can be present in urine sediment when not detectable in the blood. However, in around a quarter of cases where the child is diagnosed with mito, no mutation is detected in the mother when she is tested. This may be due to what’s known as a de novo event – a one off mutation in that single egg that was fertilised that led to the child having mito. Due to these complexities it is currently impractical to screen all women for mito.

3. How many births could be helped by the introduction of mitochondrial donation?

Based on studies from the UK and extrapolated to the Australian context, the Mito Foundation estimates about 56 births per year in Australia are at high risk of having a child with mito.

Only a proportion of those would be wanting to access mito donation as current options are suitable for some couples, including prenatal diagnosis, preimplantation genetic diagnosis or using a full donor egg for IVF. These may be the preferred options for a woman depending on her circumstances and in many cases a woman may need to try one of these options first before being able to access mitochondrial donation.

4. How will babies be monitored for complications?

There has been extensive research done in the UK to ensure this technique is as safe as possible. The first families to use the technique in Australia would be part of a clinical trial. In the UK model families gave consent for samples such as umbilical cord and the newborn blood screening spots to be kept for pathology testing. This looked for the mutation that the mother had to see if it had been passed to the child – and how much of that mutated DNA the child had received. During their development a child would have some extra tests but these would be done with the normal checks that children receive in their early life, checking again for the presence of the mutation and any change in the amount of that DNA.

Australia is well regarded as a leading nation in mitochondrial diagnosis and IVF technologies. This technique requires significant expertise in molecular testing and reproductive biology. The Senate committee examined the provision of pathology services and were reassured that the accreditation and quality systems that Australian pathology laboratories adhere to are first class. This would enable the ground-breaking technique of mitochondrial donation to become a reality for Australian families.

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What is mito?

Mitochondria are found within our cells, and are responsible for burning food to create energy. Mitochondrial disease is an umbrella term for a family of diseases, caused by defects in energy production, which powers all the organs and systems in our body. So, it is not surprising that mitochondrial disease can affect people in a number of ways and with a broad range of disease severity.

What are the symptoms?

All our organs require a constant supply of energy to function and due to the range of genetic changes that can cause mito, symptoms can vary greatly from person to person.

Mitochondrial disease may manifest at any age, though typically those who experience symptoms at a younger age have more severe health issues.

The confusion around this and the difficulties with reaching an accurate diagnosis swiftly, have prompted the Mito Foundation to create the Maybe It’s Mito campaign. They urge people who have symptoms involving 3 or more organs plus any red flag symptoms including diabetes, seizures and ‘salt and pepper’ retinopathy, to discuss mito with their doctor.

How is mito diagnosed?

Pathology testing plays a very significant role in diagnosing mito and many people undergo a diagnostic odyssey which involves extensive testing and for some people can take many months or even years.

Testing for mito

Our body’s preferred way to make energy is aerobic energy production, which takes place in the mitochondria, miniature ‘power stations’ inside our cells. It uses breakdown products from foods combined with oxygen, to produce ATP (adenosine triphosphate), the body’s primary source of energy.

Anaerobic energy production is the process by which energy is produced by breaking down foods without using any oxygen. During this process lactic acid (also called lactate) is produced by tissues.

One of the steps a doctor might take if mito is suspected is ordering a test to measure the level of lactate, which in people not affected by mito is usually present in the blood at only low levels. A high lactate level infers the body is relying more on anaerobic energy production and is not producing enough energy in the mitochondria, which could be indicative of a mitochondrial condition.

The liver may also be affected by mito, so liver function tests may also be ordered to look for evidence of liver damage.

Brain MRI and proton magnetic resonance spectroscopy (MRS) may be used to look for evidence of mitochondrial disease.

Depending on the details of each case, other pathology tests may be performed such as a lumbar puncture or a muscle biopsy.

If mutations in a specific gene are known to be responsible for a specific type of mitochondrial disease, then DNA sequencing can be performed to identify those gene mutations.

Professor John Christodoulou is Co-Leader of the Brain and Mitochondrial Research Group at the Murdoch Children’s Research Institute and sits on the Mito Foundation’s Scientific and Medical Advisory Panel. He said, “The catchcry we use to describe mito is ‘any symptom, any age, any organ, any inheritance’ because the way the disease affects people is so broad. It’s very important to understand that about mito.

This is why it can be difficult to diagnose quickly and studies are being done to gather evidence to improve the testing process. Using next generation DNA sequencing earlier in the diagnostic journey could help reduce the time taken to diagnosis and reduce the number of pathology tests and imaging procedures needed. This would help patients get the right treatment sooner.”

How do you get mito?

Changes in either nuclear or mitochondrial DNA can cause mito, and in most cases are passed on from parents to their children.  Depending on the inheritance pattern, a number of members of the family may show clinical signs of mito, although the severity of symptoms can vary greatly between family members.

Mitochondrial disease often requires a triggering event in order for symptoms to appear, which may include an infection or surgery. Due to the higher level of energy required, periods of intense exercise can also be a trigger.

For more information about mitochondrial disease visit mito.org.au

The post Mito mysteries: what is mitochondrial disease and how is it diagnosed? first appeared on Know Pathology Know Healthcare.

Learn more about Mito Foundation

The Role of Pathology in Mitochondrial Disease (mito)

Pathology plays an important role in both the diagnosis and ongoing management of mito. Patients can experience a wide variety of symptoms and it can be challenging to join the dots and consider mitochondrial disease as the cause. Patients often undergo a multitude of blood tests as part of their journey to diagnosis. Ongoing symptom management also involves regular pathology services over the patient’s lifetime.

Exciting research may lead to developments in pathology testing that improve the diagnostic process for people with mito, avoiding patients having to undergo invasive, painful and often inconclusive muscle and liver biopsies.

The post Mito Foundation first appeared on Know Pathology Know Healthcare.

The organization was founded in 2009 to support mito patients and their families via community activities, advocacy and education, whilst supporting research into diagnosis and treatment in the hope that this will translate into preventions and cures.

So what is mitochondrial disease?

Mitochondria are bean-shaped organelles that float freely inside almost every cell in our body. They have a double membrane – the site of various biochemical reactions, including cellular respiration – the process of converting carbohydrates, fats, and proteins into fuel for cells.

They may be small but each mitochondria requires more than 1400 genes to create it.  Mitochondrial disease (‘mito disease’ for short) is due to a fault in one or more of these genes. Since high energy organs require so many mitochondria within their cells, they are usually the first to be affected in mitochondrial disease. These include the brain, nerves, muscles, eyes, ears, heart, bowels, liver, kidney and pancreas.

Symptoms range from fatigue and weakness to developmental delays, dementia, seizures, movement disorders, blindness and gastrointestinal conditions such as indigestion.

According to recent Australian studies about 1 in 200 people will carry a mitochondrial genetic defect – nearly 120,000 Australians. Not all of these people will develop the illness but the risk of developing serious illness is about 1 in 5,000.

Given the range of organs and functions potentially affected, mitochondrial diseases are difficult to diagnose but they can be made through a combination of clinical observations, diagnostic imaging, and pathology tests including blood tests and muscle biopsies.

There is currently no cure for mito disease but there are treatments and therapies that can alleviate symptoms and slow the progression of the disease, so an accurate diagnosis is important.

The research carried out with the support of AMDF will hopefully make diagnosis easier for future patients. This month, for example, AMDF teamed up with the Australian Genomics Health Alliance to conduct genetic screening on people with suspected mito disease.

The partnership will ensure that all those with suspected mito will have access to genetic testing via a blood test and a conclusive diagnosis – without which fifty per cent of people would have been subject to inconclusive and invasive tests and potentially still no diagnosis.

To find out more about mito disease and the Foundation’s important work in helping patients, you can check out their website here.

The post A genetic defect carried by 1 in 200 people – mitochondrial disease first appeared on Know Pathology Know Healthcare.